title: Simvastatin increases ADAMTS13 expression in podocytes.
abstract: BACKGROUND
  ADAMTS13 is a specific von Willebrand factor-cleaving protease. Severe deficiency of ADAMTS13 is the main cause of thrombotic thrombocytopenic purpura. ADAMTS13 is mainly synthesized and released from hepatic stellate cells and endothelial cells, but is also expressed in other cells, including kidney podocytes. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has a beneficial effect on atherosclerosis and also has anti-inflammatory and antithrombotic properties. A recent study indicates that ADAMTS13 reduces inflammatory plaque formation during early atherosclerosis in mice. In our study, we investigated the effects of simvastatin on inflammatory cytokines-induced ADAMTS13 expression in podocytes.
  
  
  METHODS
  A conditionally immortalized mouse podocyte cell line was utilized to study the expression of ADAMTS13 in podocytes. The influence of TNF-α, IL-4, IL-6 and simvastatin on ADAMTS13 was investigated. ADAMTS13 mRNA levels in podocytes were measured by using real-time PCR and protein levels were detected by Western blotting.
  
  
  RESULTS
  Simvastatin significantly up-regulated the expression levels of ADAMTS13 mRNA and protein in podocytes. IL-6 decreased ADAMTS13 expression, and TNF-α had no significant effects on ADAMTS13 expression in podocytes. IL-4 reduced ADAMTS13 mRNA expression but not its protein level. Simvastatin was able also reversed the inhibitory effect of IL-6.
  
  
  CONCLUSIONS
  We demonstrate that simvastatin increases the expression of ADAMTS13 in a dose-dependent manner in podocytes, which likely contributes to the antithrombotic property of statin. Different inflammatory cytokines have different effects on the levels of ADAMTS13 mRNA expression and protein within podocytes.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Guoyuan
authors.initials: G
authors.lastname: Lu
authors.forename: Ningzheng
authors.initials: N
authors.lastname: Dong
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Ma
authors.forename: Changgeng
authors.initials: C
authors.lastname: Ruan
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000276:immunology; D000071120:ADAMTS13 Protein; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D050199:Podocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D019821:Simvastatin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D019821:Simvastatin; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: 3-hydroxy-3-methylglutaryl coenzyme A; A disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13; ADAMTS13; HMG-CoA; IL-4; IL-6; TNF-α; TTP; VWF; interleukin-4; interleukin-6; podocyte; simvastatin; thrombotic thrombocytopenic purpura; tumor necrosis factor-α; von Willebrand factor